The structure of Canagliflozin, i.e. (1S)-1,5-dehydro-1-C-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D-glucitol, is shown as formula III. This medicament is developed by Janssen Pharmaceutical Ltd., a subsidiary of Johnson & Johnson Pharmaceutical Ltd., and approved by FDA on Mar. 29, 2013 as an antihyperglycemic for treating type II diabetes. It is the first sodium-glucose-cotransporter 2 (SGLT2) inhibitor approved by FDA. According to the market share of canagliflozin, the continuously rising number of diabetes patients, and the increasing difficulty of glycemic control for patients, analysts predict that the sales of this medicament will be over 600 million USD till 2016. 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene, the structure of which is shown as formula I, is an important intermediate for synthesizing canagliflozin. Thus, in view of the market prospect of canagliflozin, it is very necessary to study the synthesis of 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene.

Chinese Patent Application CN103214471A reports that 2-(2-methyl-5-bromobenzyl)-5-(4-fluorophenyl)thiophene is obtained by a reduction reaction using (5-bromo-2-methylphenyl)[5-(p-fluorophenyl)thiophene-2-yl]methanone as raw material, under the reaction condition of the raw material being treated with a silicane reagent (triethyl silicane, etc.) in a proper solvent (such as acetonitrile, dichloromethane, etc.) in the presence of an acid (BF3.Et2O, or trifluoroacetic acid, methanesulfonic acid, etc.), or being treated with hydrazine hydrate at high temperature under rare gas atmosphere in a proper solvent (such as ethylene glycol, etc.) in the presence of a base. In one aspect, this method requires silicane reagent, which is expensive, inflammable and has irritating smells; it has low yield of only 78%; and moreover, it requires purification by chromatography, thus the post-treatment is complicated. In another aspect, if hydrazine hydrate is used for the reduction treatment, a rare gas atmosphere is required for performing the method, so that the reaction condition is harsh, which is not suitable for industrial production; in addition, a high temperature of 190° C. is required for performing the method, resulting in high power consumption, and high costs.
